miR-21 mediates nickel nanoparticle-induced pulmonary injury and fibrosis.
miR-21 mediates nickel nanoparticle-induced pulmonary injury and fibrosis.
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miR-21介导镍纳米颗粒诱导的肺损伤和纤维化。
DOI：
10.1080/17435390.2020.1808727
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发表时间：
2020-11
期刊：
影响因子：
5
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Mo Y;Zhang Y;Wan R;Jiang M;Xu Y;Zhang Q
我们和其他研究小组已经证明，暴露于镍纳米颗粒（Nano-Ni）会导致严重和持续的肺部炎症和纤维化，但潜在的机制尚不清楚。在这里，我们提出miR-21可能在纳米镍诱导的肺部炎症、损伤和纤维化中发挥重要作用。我们的剂量和时间反应研究表明，C57BL/6J （WT）小鼠暴露于纳米镍会导致miR-21、促炎细胞因子和促纤维化介质的上调。组织学上，纳米镍暴露引起严重的肺部炎症和纤维化。基于剂量和时间反应研究，我们选择每只小鼠50 μg的纳米ni剂量来比较纳米ni对WT和miR-21 KO小鼠肺的影响。在暴露后第3天，纳米镍引起了严重的急性肺部炎症和损伤，反映在WT小鼠肺组织BALF中中性粒细胞计数、CXCL1/KC水平、LDH活性、总蛋白浓度、MMP-2/9蛋白水平和活性以及促炎细胞因子的增加，组织学证实了这一点。虽然Nano-Ni对miR-21 KO小鼠具有类似的作用，但上述水平明显低于WT小鼠。在组织学上，纳米镍暴露的WT小鼠肺肺泡间隙和间质组织中有大量多形核细胞（PMN）和巨噬细胞浸润。然而，miR-21 KO小鼠暴露于纳米ni仅引起轻度急性肺部炎症和损伤。暴露后第42天，纳米镍引起WT小鼠肺部广泛的肺纤维化和慢性炎症。然而，miR-21 KO小鼠暴露于纳米ni仅引起轻度肺纤维化和慢性肺炎症。我们的研究结果还表明，暴露于纳米ni可引起WT和miR-21 KO小鼠肺中TGF-β1、phospho-Smad2、COL1A1和COL3A1的上调。然而，除了TGF-β1在两种小鼠中相似外，miR-21 KO小鼠的水平明显低于WT小鼠。Smad7在WT小鼠肺中表达降低，而在miR-21 KO小鼠肺中未见表达降低。我们的研究结果表明，敲除miR-21可以改善纳米镍诱导的肺部炎症、损伤和纤维化，这表明miR-21在纳米镍诱导的肺毒性中发挥重要作用。
We and other groups have demonstrated that exposure to nickel nanoparticles (Nano-Ni) results in severe and persistent lung inflammation and fibrosis, but the underlying mechanisms remain unclear. Here, we propose that miR-21 may play an important role in Nano-Ni-induced lung inflammation, injury, and fibrosis. Our dose- and time-response studies demonstrated that exposure of C57BL/6J (WT) mice to Nano-Ni resulted in upregulation of miR-21, proinflammatory cytokines, and profibrotic mediators. Histologically, exposure to Nano-Ni caused severe pulmonary inflammation and fibrosis. Based on the dose- and time-response studies, we chose a dose of 50 μg of Nano-Ni per mouse to compare the effects of Nano-Ni on WT with those on miR-21 KO mouse lungs. At day 3 post-exposure, Nano-Ni caused severe acute lung inflammation and injury that were reflected by increased neutrophil count, CXCL1/KC level, LDH activity, total protein concentration, MMP-2/9 protein levels and activities, and proinflammatory cytokines in the BALF or lung tissues from WT mice, which were confirmed histologically. Although Nano-Ni had similar effects on miR-21 KO mice, the above mentioned levels were significantly lower than those in WT mice. Histologically, lungs from WT mice exposed to Nano-Ni had infiltration of a large number of polymorphonuclear (PMN) cells and macrophages in the alveolar space and interstitial tissues. However, exposure of miR-21 KO mice to Nano-Ni only caused mild acute lung inflammation and injury. At day 42 post-exposure, Nano-Ni caused extensive pulmonary fibrosis and chronic inflammation in the WT mouse lungs. However, exposure of miR-21 KO mice to Nano-Ni only caused mild lung fibrosis and chronic lung inflammation. Our results also showed that exposure to Nano-Ni caused upregulation of TGF-β1, phospho-Smad2, COL1A1, and COL3A1 in both WT and miR-21 KO mouse lungs. However, levels were significantly lower in miR-21 KO mice than in WT mice, except TGF-β1, which was similar in both kinds of mice. Decreased expression of Smad7 was observed in WT mouse lungs, but not in miR-21 KO mice. Our results demonstrated that knocking out miR-21 ameliorated Nano-Ni-induced pulmonary inflammation, injury, and fibrosis, suggesting the important role of miR-21 in Nano-Ni-induced pulmonary toxicity.
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影响因子：
24.3
作者：
Gushima, Y;Ichikado, K;Ando, M
通讯作者：
Ando, M
影响因子：
2.8
作者：
Åkerlund E;Cappellini F;Di Bucchianico S;Islam S;Skoglund S;Derr R;Odnevall Wallinder I;Hendriks G;Karlsson HL
通讯作者：
Karlsson HL
影响因子：
46.9
作者：
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通讯作者：
Colvin, VL
影响因子：
17.1
作者：
Guinea-Viniegra, Juan;Jimenez, Maria;Wagner, Erwin F.
通讯作者：
Wagner, Erwin F.
影响因子：
2.1
作者：
Dick, CAJ;Brown, DM;Stone, V
通讯作者：
Stone, V